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Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease
Parkinson’s disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) i...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311784/ https://www.ncbi.nlm.nih.gov/pubmed/32625117 http://dx.doi.org/10.3389/fphys.2020.00653 |
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author | Lavin, Kaleen M. Ge, Yongchao Sealfon, Stuart C. Nair, Venugopalan D. Wilk, Katarzyna McAdam, Jeremy S. Windham, Samuel T. Kumar, Preeti Lakshman McDonald, Merry-Lynn N. Bamman, Marcas M. |
author_facet | Lavin, Kaleen M. Ge, Yongchao Sealfon, Stuart C. Nair, Venugopalan D. Wilk, Katarzyna McAdam, Jeremy S. Windham, Samuel T. Kumar, Preeti Lakshman McDonald, Merry-Lynn N. Bamman, Marcas M. |
author_sort | Lavin, Kaleen M. |
collection | PubMed |
description | Parkinson’s disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson’s disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms. Our objective was to identify transcriptional networks that may contribute to RT-induced neuromuscular remodeling in PD. We generated transcriptome-wide skeletal muscle RNA-sequencing in 5 participants with PD [4M/1F, 67 ± 2 years, Hoehn and Yahr stages 2 (n = 3) and 3 (n = 2)] before and after 16-week high intensity RT to identify transcriptional networks that may in part underpin RT-induced neuromuscular remodeling in PD. Following RT, 304 genes were significantly upregulated, notably related to remodeling and nervous system/muscle development. Additionally, 402 genes, primarily negative regulators of muscle adaptation, were downregulated. We applied the recently developed Pathway-Level Information ExtractoR (PLIER) method to reveal coordinated gene programs (as latent variables, LVs) that differed in skeletal muscle among young (YA) and old (OA) healthy adults and PD (n = 12 per cohort) at baseline and in PD pre- vs. post-RT. Notably, one LV associated with angiogenesis, axon guidance, and muscle remodeling was significantly lower in PD than YA at baseline and was significantly increased by exercise. A different LV annotated to denervation, autophagy, and apoptosis was increased in both PD and OA relative to YA and was also reduced by 16-week RT in PD. Thus, this analysis identified two novel skeletal muscle transcriptional programs that are dysregulated by PD and aging, respectively. Notably, RT has a normalizing effect on both programs in individuals with PD. These results identify potential molecular transducers of the RT-induced improvements in neuromuscular remodeling and motor function that may aid in optimizing exercise rehabilitation strategies for individuals with PD. |
format | Online Article Text |
id | pubmed-7311784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73117842020-07-02 Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease Lavin, Kaleen M. Ge, Yongchao Sealfon, Stuart C. Nair, Venugopalan D. Wilk, Katarzyna McAdam, Jeremy S. Windham, Samuel T. Kumar, Preeti Lakshman McDonald, Merry-Lynn N. Bamman, Marcas M. Front Physiol Physiology Parkinson’s disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson’s disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms. Our objective was to identify transcriptional networks that may contribute to RT-induced neuromuscular remodeling in PD. We generated transcriptome-wide skeletal muscle RNA-sequencing in 5 participants with PD [4M/1F, 67 ± 2 years, Hoehn and Yahr stages 2 (n = 3) and 3 (n = 2)] before and after 16-week high intensity RT to identify transcriptional networks that may in part underpin RT-induced neuromuscular remodeling in PD. Following RT, 304 genes were significantly upregulated, notably related to remodeling and nervous system/muscle development. Additionally, 402 genes, primarily negative regulators of muscle adaptation, were downregulated. We applied the recently developed Pathway-Level Information ExtractoR (PLIER) method to reveal coordinated gene programs (as latent variables, LVs) that differed in skeletal muscle among young (YA) and old (OA) healthy adults and PD (n = 12 per cohort) at baseline and in PD pre- vs. post-RT. Notably, one LV associated with angiogenesis, axon guidance, and muscle remodeling was significantly lower in PD than YA at baseline and was significantly increased by exercise. A different LV annotated to denervation, autophagy, and apoptosis was increased in both PD and OA relative to YA and was also reduced by 16-week RT in PD. Thus, this analysis identified two novel skeletal muscle transcriptional programs that are dysregulated by PD and aging, respectively. Notably, RT has a normalizing effect on both programs in individuals with PD. These results identify potential molecular transducers of the RT-induced improvements in neuromuscular remodeling and motor function that may aid in optimizing exercise rehabilitation strategies for individuals with PD. Frontiers Media S.A. 2020-06-17 /pmc/articles/PMC7311784/ /pubmed/32625117 http://dx.doi.org/10.3389/fphys.2020.00653 Text en Copyright © 2020 Lavin, Ge, Sealfon, Nair, Wilk, McAdam, Windham, Kumar, McDonald and Bamman. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Lavin, Kaleen M. Ge, Yongchao Sealfon, Stuart C. Nair, Venugopalan D. Wilk, Katarzyna McAdam, Jeremy S. Windham, Samuel T. Kumar, Preeti Lakshman McDonald, Merry-Lynn N. Bamman, Marcas M. Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title | Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_full | Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_fullStr | Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_full_unstemmed | Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_short | Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease |
title_sort | rehabilitative impact of exercise training on human skeletal muscle transcriptional programs in parkinson’s disease |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311784/ https://www.ncbi.nlm.nih.gov/pubmed/32625117 http://dx.doi.org/10.3389/fphys.2020.00653 |
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